(+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol | 299964-35-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol
• 英文别名: 1-(4'-benzyloxy-3'-nitro)phenyl-2-bromoethanol；1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol；3-nitro-4-benzyloxy-α-(bromomethyl)-benzylalcohol；2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol；2-bromo-1-(3-nitro-4-phenylmethoxyphenyl)ethanol
• CAS: 299964-35-5
• 化学式: C₁₅H₁₄BrNO₄
• 分子量: 352.184
• InChiKey: HQGAJOFIQLBIIM-UHFFFAOYSA-N

物化性质

• 沸点：
  493.9±45.0 °C(Predicted)
• 密度：
  1.529±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol 在 10% palladium on active carbon 吡啶 、 盐酸 、 aluminum oxide 、 lipase PS Celite-immobilized 、 氢气 、 铁粉 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 168.75h， 生成 福莫特罗
  参考文献：
  名称：

  An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases

  摘要：

  0The potent beta(2)-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00238-x
• 作为产物：
  描述：

  氯化苄 在 sodium tetrahydroborate 、 溴 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 丙酮 为溶剂， 生成 (+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol
  参考文献：
  名称：

  Design, synthesis and evaluation of dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors

  摘要：

  A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology beta(2)-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high beta(2)-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R, R)-11c, exhibited agonist (EC50 = 1.05 nM, pEC(50) = 9.0) and potent PDE4B2 inhibitory activities (IC50 = 0.092 mu M). (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.11.028

文献信息

• Process for the preparation of tricyclic amino alcohol derivatives
  申请人：ASAHI KASEI KABUSHIKI KAISHA

  公开号：US20030225289A1

  公开（公告）日：2003-12-04

  A process for the preparation of tricyclic amino alcohol derivatives including 2-[N-[2-(9H-carbazol-2-yloxy)ethyl]]amino-1-[(3-methylsulfonylamino)phenyl]ethanol useful in the treatment of diabetes, obesity, hyperlipidemia and so on; and intermediates as represented by formula (5) or (6) or the like useful in the preparation, wherein R11 is hydrogen or the like; and *1 represents an asymmetric carbon atom. 2-Halo-1-(3-nitrophenyl)ethanone derivatives and 1-(3-nitrophenyl)oxirane derivatives, which are intermediates for the preparation of tricyclic amino alcohol derivatives, are easy of purification, and particularly optically active 1-(3-nitrophenyl)oxirane derivatives are effective in enhancing the optical purities of the final products.

  一种用于制备包括2-[N-[2-(9H-咔唑-2-氧基)乙基]]氨基-1-[3-(甲磺酰氨基)苯基]乙醇在内的三环氨基醇衍生物的方法，该方法在治疗糖尿病、肥胖、高脂血症等方面有用；以及用公式(5)或(6)等表示的中间体，在制备中有用，其中R11是氢等；*1代表一个不对称碳原子。2-卤代-1-(3-硝基苯基)乙酮衍生物和1-(3-硝基苯基)环氧衍生物是用于制备三环氨基醇衍生物的中间体，易于纯化，特别是光学活性的1-(3-硝基苯基)环氧衍生物在提高最终产品的光学纯度方面是有效的。
• PURIFICATION PROCESS FOR PREPARING HIGHLY PURE ARFORMOTEROL TARTRATE SUBSTANTIALLY FREE OF DESFORMYL IMPURITY
  申请人：Jagtap Anant Kishanrao

  公开号：US20120053246A1

  公开（公告）日：2012-03-01

  Provided herein is a highly pure arformoterol tartrate or an amorphous form thereof substantially free of desformyl impurity, 2-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]aniline, process for the preparation thereof, and pharmaceutical compositions comprising the highly pure arformoterol tartrate substantially free of the desformyl impurity.

  本文提供了一种高纯度的酒石酸阿福莫特罗尔或其无定形形式，基本上不含去甲酰杂质2-羟基-5-[(1R)-1-羟基-2-[[(1R)-2-(4-甲氧基苯基)-1-甲基乙基]氨基]乙基]苯胺，以及其制备方法和包含高纯度酒石酸阿福莫特罗尔、基本上不含去甲酰杂质的药物组合物。
• Process for preparation of intermediates of arformoterol
  申请人：INKE, S.A.

  公开号：EP2348013A1

  公开（公告）日：2011-07-27

  An improved method for the preparation of optically pure isomers of Formoterol is disclosed, particularly the (R,R)-isomer. A method of preparation of substantially enantiomerically pure (R,R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[[2-(4-methoxy-phenyl)-1-methyl-ethyl]-(1-phenyl-ethyl)-amino]-ethanol to use in the production of (R,R)-Formoterol is also disclosed

  揭示了一种改进的方法，用于制备光学纯的福莫特罗异构体，特别是（R,R）-异构体。还揭示了一种制备基本对映异构体纯度高的（R,R）-1-(4-苄氧基-3-硝基苯基)-2-[[2-(4-甲氧基苯基)-1-甲基乙基]-(1-苯基乙基)-氨基]-乙醇的方法，用于生产（R,R）-福莫特罗。
• PROCESSES FOR PREPARING SUBSTANTIALLY PURE ARFORMOTEROL AND ITS INTERMEDIATES
  申请人：Dixit Girish

  公开号：US20110313199A1

  公开（公告）日：2011-12-22

  Provided herein are improved, convenient and industrially advantageous processes for the preparation of N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide (Arformoterol) or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided further herein is an improved and industrially advantageous process for the preparation of a substantially enantiomerically pure arformoterol intermediate, (R)-4-methoxy-α-methyl-N-(phenylmethyl)benzeneethanamine.

  本文提供了改进的、便捷的和在工业上具有优势的过程，用于制备N-[2-羟基-5-[(1R)-1-羟基-2-[[(1R)-2-(4-甲氧基苯基)-1-甲基乙基]氨基]乙基]苯甲酰胺（阿福莫特罗）或其药用可接受的盐，产率高，纯度高。此外，本文还提供了一种改进的、在工业上具有优势的过程，用于制备基本对映纯的阿福莫特罗中间体(R)-4-甲氧基-α-甲基-N-(苯甲基)苯乙胺。
• Bronchospasmolytic phenylethanolamines
  申请人：Pharmacia AS

  公开号：US04072760A1

  公开（公告）日：1978-02-07

  Phenylethanolamines of the formula I ##STR1## wherein R is substituted phenyl or optionally substituted furyl, thienyl, or pyridyl, R.sub.5 is hydrogen, lower alkyl, or optionally substituted benzyl, R.sub.4, R.sub.6, R.sub.8, and R.sub.9 each are hydrogen or lower alkyl, R.sub.7 is hydrogen, halogen, or lower alkyl, Q is --CO--or --CH.sub.2 --, and L is hydrogen or lower alkylcarbonyl, and enantiomers, diastereoisomers and salts thereof; also, process for preparing the compounds. Compounds of the invention possess bronchosposmolytic activity.

  公式I的苯乙醇胺##STR1##中，R为取代苯基或可选择取代的呋喃基、噻吩基或吡啶基，R.sub.5为氢、低碳基或可选择取代的苄基，R.sub.4、R.sub.6、R.sub.8和R.sub.9各自为氢或低碳基，R.sub.7为氢、卤素或低碳基，Q为--CO--或--CH.sub.2--，L为氢或低碳基酰基，以及其对映体、非对映体异构体和盐；同时，提供了制备这些化合物的方法。本发明的化合物具有支气管舒张活性。